Biocompatible, biodegradable colloidal systems for drug delivery are commonly made of either lipids or polymers (Balmayor et al., 2011, Controlled delivery systems: from pharmaceuticals to cells and genes. Pharm Res 28, 1241-1258; Bunjes, 2010, Lipid nanoparticles for the delivery of poorly water-soluble drugs. J of Pharmacy and Pharmacology 62, 1637-1645; Wong et al., 2010, Nanotechnology applications for improved delivery of antiretroviral drugs to the brain. Advanced Drug Delivery Reviews 62, 503-517). Both materials have their own advantages. While lipid colloids are inherently more efficient systems for encapsulation of the highly lipophilic compounds, and are less likely to cause toxic or immunogenic responses (Müller et al., 2000, Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations, Adv Drug Deliv Rev 54 Suppl 1, S131-155; Salvador-Morales et al., 2009, Immunocompatibility properties of lipid-polymer hybrid nanoparticles with heterogeneous surface functional groups. Biomaterials 30, 2231-2240), on comparative terms, polymeric colloids (e.g. polymeric nanoparticles) can be easily fabricated at low temperature, are able to deliver both hydrophilic and lipophilic drugs, and have uniform and reproducible size distribution and morphology (Barratt, 2003, Colloidal drug carriers: achievements and perspectives. Cell Mol Life Sci 60, 21-37; Panyam and Labhasetwar, 2003, Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Adv Drug Deliv Rev 55, 329-347). Because newer drugs tend to have high lipophilicity and these drugs often have delivery issues (Cai et al., 2010, Nanocarriers: a general strategy for enhancement of oral bioavailability of poorly absorbed or pre-systemically metabolized drugs. Curr Drug Metab 11, 197-207), the need for lipid-based systems with an improved design, possibly incorporating some advantages of polymeric systems, has become particularly strong.
Colloids made of solid lipids (e.g. solid lipid nanoparticles) and oil droplets (e.g. nanoemulsion) have been extensively studied for lipophilic delivery in recent years with promising results. However, solid lipid nanoparticles tend to slowly release their entrapped drugs for weeks, which may be unsuitable for many non-chronic disease conditions (Wong et al., 2007, Chemotherapy with anticancer drugs encapsulated in solid lipid nanoparticles. Advanced Drug Delivery Reviews 59, 491-504), whereas nanoemulsions made of fine oil droplets may encounter stability issues like Ostwald ripening as well as technical issues such as difficulty to lyophilize (Li et al., 2009, PEG-PLA diblock copolymer micelle-like nanoparticles as all-trans-retinoic acid carrier: in vitro and in vivo characterizations. Nanotechnology 20, 055106; Tadros et al., 2004, Formation and stability of nano-emulsions. Advances in Colloid and Interface Science 108-109, 303-318). Researchers are still searching for a closer-to-ideal nanocarrier, especially for the controlled delivery of lipophilic; poorly water-soluble compounds.
“Hybrid” nanotechnology has been previously developed, in which polymers are embedded into nanoparticle cores of mostly solid lipids and/or phospholipids. The polymer component enables efficient binding of hydrophilic compounds and the lipid matrix serves to control their release (Wong et al., 2006, A new polymer-lipid hybrid nanoparticle system increases cytotoxicity of doxorubicin against multidrug-resistant human breast cancer cells. Pharm Res 23, 1574-1585). The combination of the advantages of both polymers and lipids in a single nanocarrier has made this design attractive to others as well (Liu et al., 2010, Folic acid conjugated nanoparticles of mixed lipid monolayer shell and biodegradable polymer core for targeted delivery of Docetaxel. Biomaterials 31, 330-338; Zhang et al., 2008, All-trans retinoic acid (atRA) differentially induces apoptosis in matched primary and metastatic melanoma cells—a speculation on damage effect of at RA via mitochondrial dysfunction and cell cycle redistribution. Carcinogenesis 24, 185-191).
A disadvantage of drug-loaded solid lipid nanoparticles is that the solid materials tend to pack tightly and contract during solidification. This process often drives the loaded drug molecules towards the solid nanoparticle surface to increase the risk of uncontrolled initial drug releases (Wong et al., 2007, Chemotherapy with anticancer drugs encapsulated in solid lipid nanoparticles. Advanced Drug Delivery Reviews 59, 491-504). Inclusion of oil into solid lipids was found to introduce internal room or “nanostructure” within the particle cores by increasing their amorphosity, leading to more uniform drug distribution and improved drug release profiles (Muller et al., 2002, Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations. Adv Drug Deliv Rev 54 Suppl 1, S131-155).
PLGA copolymers belong to one of the very few classes of biomaterials widely approved for biomedical applications (Bala et al., 2004, PLGA nanoparticles in drug delivery: the state of the art. Crit Rev Ther Drug Carrier Syst 21, 387-422), (Astete and Sabliov, 2006, Synthesis and characterization of PLGA nanoparticles. J of Biomaterials Science, Polymer Edition 17, 247-289). Polymeric drug carriers build with PLGA are highly biocompatible and biodegradable, possess uniform and reproducible size and morphology, and have good storage and handling properties (Astete and Sabliov, 2006, Synthesis and characterization of PLGA nanoparticles. J of Biomaterials Science, Polymer Edition 17, 247-289).
There remains a need for a nanocarrier for the controlled delivery of lipophilic, poorly water-soluble compounds.